Methanol → 7-Bromo-1H-indazol-5-amine

HRID 1678239Notes

Reaction equation

HRID 1678239 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N+:11]([O-])=O)[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2.CO>C(O)(=O)C.[Fe]>[Br:1][C:2]1[CH:3]=[C:4]([NH2:11])[CH:5]=[C:6]2[C:10]=1[NH:9][N:8]=[CH:7]2

Participants

5

Reactant 2

HCID 887MethanolHCID 14819687-bromo-5-nitro-1H-indazole

Product 1

HCID 468399137-Bromo-1H-indazol-5-amineYield 40%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of iron (Aldrich 99.99+%, 13.85 g, 248.0 mmol) and crude 7-bromo-5-nitro-1H-indazole (20.00 g, 82.63 mmol) in glacial acetic acid (100 mL) was heated at about 80° C. in a 2-neck round bottom flask equipped with a mechanical stirrer and a nitrogen line with a bubbler. After about 2.5 hours, MeOH (100 mL) was added, warmed, and filtered hot through Celite®. The Celite® pad was washed with additional MeOH (4×100 mL) and the combined organic layers were concentrated under reduced pressure. The residues were basified to pH ˜7 using aqueous Na2CO3 (2M) and the product was extracted into EtOAc (1 L) over about 16 hours. The layers were separated and the aqueous layer was further extracted with additional EtOAc (3×500 mL). The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, decanted, and concentrated. The resulting solid was pre-adsorbed onto silica and purified by silica gel chromatography using heptane/EtOAc (1:1) as the eluent to afford 7-bromo-1H-indazol-5-ylamine (6.92 g, 40%); 1H NMR (DMSO-d6, 400 MHz) 12.92 (br s, 1H), 7.87 (s, 1H), 7.03 (d, J=1.6 Hz, 1H), 6.77 (d, J=1.2 Hz, 1H) 4.96 (br s, 2H); LC-MS (Table 1, Method e) Rt 0.83.

Workup

  1. customequipped with a mechanical stirrer
  2. temperaturewarmed
  3. filtrationfiltered hot through Celite®
  4. washThe Celite® pad was washed with additional MeOH (4×100 mL)
  5. concentrationthe combined organic layers were concentrated under reduced pressure
  6. extractionthe product was extracted into EtOAc (1 L) over about 16 hours
  7. customThe layers were separated
  8. extractionthe aqueous layer was further extracted with additional EtOAc (3×500 mL)
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried over anhydrous Na2SO4
  11. customdecanted
  12. concentrationconcentrated
  13. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-f3be3010102743509c6d53f7281a1f6e
Source dataset
uspto-grants-2011_08
Patent number
US08008481B2

Reaction notes

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